囊型包虫病（CE）是我国西部危害严重的人畜共患病，几乎均原发于肝脏，至今无理想治疗手段。我们前期研究发现CE病灶周围巨噬细胞(Mφ)大量浸润，细粒棘球蚴（E.g）分泌蛋白EgTPx可诱导Mφ向M2型极化，且Mφ中PI3K通路成员Akt和mTOR发生磷酸化，推测EgTPx可能通过PI3K/Akt/mTOR信号通路调控肝脏Mφ向M2型极化造成E.g免疫逃逸，但机制不明。本项目拟利用肝脏原代Mφ系、E.g动物模型和CE临床标本三个层面确定EgTPx对Mφ极化和功能的影响，并通过正向激活和反向抑制方法阐明EgTPx调控Mφ极化的分子机制；其次采用细胞清除和过继转输方式，明确肝脏Mφ在E.g感染所致免疫耐受过程中的关键作用；最后使用EgTPx中和抗体或mTOR抑制剂干预E.g感染动物模型，探索抑制肝脏Mφ向M2型极化用于CE治疗的有效性，对揭示E.g致病机制、研制新型治疗药物和方法具有重要科学意义。

Echinococcosis is a serious zoonoses in northwest of China and more than 95% cases are cytic echinococcosis (CE), which caused by Echinococcus granulosus (E.g) infection. The pathogenic mechanism of E.g need to be clarified. Study on the secretion protein of E.g in regulating liver macrophage polarization which mediated host immune tolerance is rarely reported. In our previous study, we found larger macrophages infiltration around lesions in CE patients; E.g infection and key secreted protein TPx can induce macrophages to M2 polarization, and the key member Akt and mTOR of PI3K signaling pathway in M2 macrophage occur phosphorylation, suggesting that TPx may induce host immune tolerance by regulating macrophage polarization through the PI3K/Akt/mTOR signal pathway, but the mechanism is unknown. In this work, we plan to elucidate the effects of the key secreted protein EgTPx on macrophage polarization type and function influence through using the liver primary macrophages, E.g infection animal models and CE clinical specimens. Using EgTPx stimulation and the inhibitor of mTOR in liver macrophage cultivation system in vitro to identify the molecular mechanism of macrophage polarization. Secondly, establishing a E.g infection mice model, we elucidate the key role in immune tolerance of liver macrophages in E.g infection by way of reverse cell clearance and forward adoptive transfer. Finally, we explore the feasibility and effectiveness for CE treatment by inhibit liver macrophages toward to M2 polarization through using the EgTPx neutralizing antibody or mTOR inhibitor in the E.g infected mice model in vivo. These studies have important scientific significance to reveal the mechanism of growth, development and pathogenicity of E.g and to develop new drugs and new therapeutic method for CE.